Pulmonary alveolar proteinosis caused by deletion of the GM-CSFRalpha gene in the X chromosome pseudoautosomal region 1.
Pulmonary alveolar proteinosis (PAP) is a rare lung disorder in which surfactant-derived lipoproteins accumulate excessively within pulmonary alveoli, causing severe respiratory distress. The importance of granulocyte/macrophage colony-stimulating factor (GM-CSF) in the pathogenesis of PAP has been confirmed in humans and mice, wherein GM-CSF signaling is required for pulmonary alveolar macrophage catabolism of surfactant. PAP is caused by disruption of GM-CSF signaling in these cells, and is usually caused by neutralizing autoantibodies to GM-CSF or is secondary to other underlying diseases. Rarely, genetic defects in surfactant proteins or the common beta chain for the GM-CSF receptor (GM-CSFR) are causal. Using a combination of cellular, molecular, and genomic approaches, we provide the first evidence that PAP can result from a genetic deficiency of the GM-CSFR alpha chain, encoded in the X-chromosome pseudoautosomal region 1.
Martinez-Moczygemba
Margarita
M
Department of Medicine, Texas A&M College of Medicine, Texas A&M Health Science Center, Houston, TX 77030, USA.
Doan
Minh L
ML
Elidemir
Okan
O
Fan
Leland L
LL
Cheung
Sau Wai
SW
Lei
Jonathan T
JT
Moore
James P
JP
Tavana
Ghamartaj
G
Lewis
Lora R
LR
Zhu
Yiming
Y
Muzny
Donna M
DM
Gibbs
Richard A
RA
Huston
David P
DP
D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D002675:Child, Preschool; D041321:Chromosomes, Human, X / Q000235:genetics*; D005091:Exons; D005260:Female; D005838:Genotype; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008297:Male; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D011649:Pulmonary Alveolar Proteinosis / Q000235:genetics*; D011663:Pulmonary Surfactants / Q000378:metabolism; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D015398:Signal Transduction / Q000502:physiology; D014424:Turner Syndrome
D039481:CD11b Antigen; C521678:CSF2RA protein, human; D011663:Pulmonary Surfactants; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor